Investigators Elucidate Genetic Differences in Those Who Develop Meningitis

Study found variations around genes that regulate the complement system.!--h2>

Genetic differences that make some people more susceptible than others to meningococcal meningitis and septicemia have been revealed in a study of over 6,000 people published in Nature Genetics. The research, led by Imperial College London and the Genome Institute of Singapore, suggests that people who develop these diseases have innate differences in their natural defenses that leave them unable to successfully attack meningococcal bacteria.

Meningococcal bacteria cause meningococcal meningitis, and meningococcal septicemia is a type of blood poisoning that accompanies this form of meningitis. Most people carry the meningococcal bacteria in their throat intermittently during their lives without ever developing the disease.

"Although most of us have carried the meningitis bacteria at some point, only around one in 40,000 people develop meningococcal meningitis,” points out professor Michael Levin, from the department of pediatrics at Imperial College London, who led the international research effort. "Our study set out to understand what causes this small group of people to become very ill while others remain immune. Our findings provide the strongest evidence so far that there are genetic factors that lead to people developing meningitis."

The research compared the genetic makeup of 1,500 people who developed meningococcal meningitis from the U.K., The Netherlands, Austria, and Spain. Over 5,000 healthy controls were enrolled as well from the Wellcome Trust Case Control Consortium. The investigators report that they looked at half a million common genetic variants across each person's genome and searched for differences between the patients and healthy controls.

The results revealed that those who had developed meningococcal meningitis had genetic markers in a number of genes involved in attacking and killing invading bacteria. The variations were around the genes for Factor H and Factor H-related proteins. These proteins regulate a part of the body's immune system called the complement system, which recognizes and kills invading bacteria.

Normally, Factor H and Factor H-related proteins ensure that the complement system does not cause excessive damage to the body's own cells. However, meningococcal bacteria can hijack the body's Factor H and use it to ensure that the body does not recognize the bacteria as foreign.

The researchers are now keen to investigate precisely how the genetic variations that they have uncovered affect the activity of Factor H and Factor H-related proteins.